We have developed a novel technique, using an irreversible antagonist, to investigate dopamine receptor turnover and find that old rats have an approximately three-fold slower rate of receptor recovery. This decreased receptor turnover may be partially responsible for some of the behavioral manifestations of aging and may be amenable to pharmacological manipulation. We will confirm these findings and investigate the effects of receptor up-regulation (following chronic reserpine) and receptor down-regulation (following chronic amphetamine) on receptor turnover rates. As such, these studies could have direct clinical relevance. The diminished CNS function which occurs with aging is accompanied by non-uniform alterations in various neurotransmitter systems. Deficits in pre- and postsynaptic dopaminergic function have been reported with age, which may underlie the increased susceptibility to extrapyramidal side effects of drugs and the increased prevalence of Parkinson's disease and other neurologic and psychiatric disorders. We have previously shown that postsynaptic receptor changes (supersensitivity) occur in response to both dopaminergic denervation and receptor blockade, and others have shown that these changes are modified in the aged animal. Dopamine receptor binding studies thus provide and ideal system in which to investigate how such homeostatic mechanisms are altered in aged animals.